Summary Functional mechanical loading has been known to play an important role in healing of fractured bones. Studies on low magnitude, high frequency (LMHF) loading (tens of micro-strains and ~30 Hz) also show improved bone regeneration. Additionally, the use of low intensity pulsed ultrasound (LIPUS) at fractured bone sites shows mechanical vibrations at ultrasound frequency can also significantly improve fractured and nonunion bone healing outcomes. While these mechanical loading regimes, with vast differences in loading magnitudes and frequencies, have been extensively investigated and their working mechanisms explored on an individual basis, a comprehensive understanding of the cumulative effects of these loading regimes is still lacking due to the limitations imposed by current load application techniques. For example, ultrasound is not capable of providing a static or low frequency load on the healing site, while direct functional loading methods typically involve only static loading. The goal of this project is to develop a bone fixation plate that utilizes an integrated actuator and sensor based on magnetoelastic (ME) materials which change in physical dimension from tens of nanometers to a few microns depending on the strength of an externally applied magnetic field. The force produced by the ME actuator is transferred to the bone fixation plate which acts directly on the bone-implant interface, resulting in extremely focused and localized loading. The externally controlled mechanical loading and real-time sensor feedback will create a valuable interface for investigating the effect of various types of mechanical stimulus on bone healing. Specifically, this project will focus on osteogenesis and vascularization in large segmental bone defects in rats. The focus of this project is to (1) develop a device that can generate variable mechanical loads on large bone defects in rats and (2) to conduct an in vivo study assessing the effects of different types of mechanical loading on vascularization and osteogenesis.